Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study.

Marios Charalambous,Daniele Corlazzoli,Johannes Erath,Laura Porcarelli,John H Rossmeisl,Andrea Tipold,An Vanhaesebrouck,Holger A Volk,Luc Van Ham,Gualtiero Gandini,Simon Platt,Francesca Cozzi,Joan R Coates,Rodolfo Cappello,Federica Tirrito,Luisa De Risio,Daisuke Hasegawa,Theresa E Pancotto ,A Gallucci ,Mihai Musteață ,Bart J G Broeckx ,Enrice I Huenerfauth ,Sofie Bhatti

doi:10.1111/jvim.15627

Abstract

BackgroundThe intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail.ObjectivesTo compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs.AnimalsClient‐owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus.MethodsRandomized parallel group clinical trial. Patients were randomly allocated to the IN‐MDZ (n = 21) or IV‐MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for ≥10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at α < .05.ResultsIN‐MDZ and IV‐MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN‐MDZ and IV‐MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN‐MDZ (100 seconds) was superior (P = .04) to IV‐MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN‐MDZ and IV‐MDZ, respectively.Conclusions and Clinical ImportanceBoth routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account.

Highlights

Status epilepticus is an emergency that requires rapid and effective delivery of anti-seizure drugs
Based on clinical trials, which evaluated the efficacy of IN-MDZ, it was concluded that IN-MDZ was effective and safe for terminating status epilepticus in humans and that it can be used by clinicians in the hospital environment and by families at home.[22,31]
Our results indicate that both IN and IV administration of MDZ are effective and safe methods for the management of status epilepticus in dogs

Summary

Introduction

Status epilepticus is an emergency that requires rapid and effective delivery of anti-seizure drugs. Because of the anatomical and physiological properties of the nasal cavity as well as its potential to circumvent the blood-brain barrier (BBB), the intranasal (IN) route might offer an advantageous and novel way to directly and quickly deliver drugs to the brain to treat various disorders.[1,2,3,4,5,6,7] Intranasal drug delivery has been widely investigated for anesthetic purposes, and experimental studies have reported that it can be effectively used for analgesia (IN-fentanyl),[8] sedation (IN-xylazine,[9] IN-medetomidine/ketamine,[10] IN-ketamine,11,12) and sedation and opioid reversal (IN-atipamezole/IN-naltrexone).[13]. The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. This notice is included in the online version to indicate that has been corrected 11 October 2019

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